Hydrogenation of amides



Patented Jan. 10, 1939 PATENT OFFICE 2.143.751 HYDROGENATION 0F Amnns Homer Adkins, Madison, Wis., assignor to Riihm a Haas Company, Philadelphia, Pa.

No Drawing. Application December 31, 1984, Se-

rial No. 760,023. In Great Britain January 2,

27 Claims.

This invention relates to a process for the hydrogenation of amides to amines.

A useful process for the reduction of amides to amines has apparently not been described. Maihle (Bull. Soc. Chim., (3) 35, 614 (1906)) reported the formation of ethyl and dimethyl amines from acetamide and of propyl and dipropylamines from propionamide in the vapor phase, Ni+Hz), but no details as to yields or purity of products were given. Guerbet (Zent..

1899 II 623) reported the formation of ethylaminefrom acetamide (Na-i-ROH), but Bouveault and Blanc (Compt. Rend, 138, 148 (1904)) obtained alcohols as the chief product from amides under similar conditions.

The transformation does not take place readily and is likely to go incompletely because the water formed in the reaction hydrolyzes unchanged amide with the formation of acid and ammonia. In the case of certain catalysts, this results in deactivation. It has now been found possible to bring about this reaction over a catalyst comprising copper oxide and chromium oxide. It has been found advantageous to use a reaction medium in which the water formed in the reaction is diluted and the hydrolysis of the amide rendered negligible. Dioxane (diethylene dioxide) is one of the media which can be used for this purpose.

The amides referred to above were prepared by the reaction of anhydrous ammonia or amines with an ester at 250 C.

Instead of using the amides themselves, it is also possible to use the ammonium salt of any given acid or the substituted ammonium salt, since these will be dehydrated with the consequent formation of the corresponding amide under the conditions of hydrogenation. It is also possible to use the acid and ammonia or substituted ammonia as the starting materials,

since these will first combine to form the salt and subsequently dehydrate as indicated above.

The catalysts used in this process comprise in general, mixtures of oxides of hydrogenating metals with oxides of acid-forming metals with or without oxides of alkali and/or alkaline earth metals. The hydrogenating metalsreferred to, comprise copper, zinc, cadmium and silver. The acid-forming metals include chromium, vanadium and molybdenum. It has been found that catalysts containing an oxide of a hydrogenating metal and an oxide of an acid-forming. metal l give particularly good results when used withan cium, and magnesium.

In the following examples, which are given by way of illustration and not limitation, the catalyst employed contained oxides of copper and chromium. Other hydrogenating metal oxides or mixtures, such as mentioned above, can be employed as can also oxides of other acid-forming metals. T

The catalytic materials can be prepared by a simple mechanical mixture of the oxides or by precipitation from solutions of the nitrates. Other methods of preparation can be employed for the making of the catalyst, since it is only important to obtain an intimate mechanical mixture or chemical combination of the oxides.

In carrying out the hydrogenations, it has been found desirable to employ a solvent in which water and the amide are soluble and which will not alkylate the amine or bring about cleavage of the amide or deactivate the catalyst. Dioxane has been found to be particularly suitable for the reaction, but other solvents possessing the above characteristics can be employed.

Example 1.-53 g. of N-laurylpiperidine.

l CuHzsCNCiHn with 9 g. of a mixture of copper-oxide chromiumoxide, as a catalyst was allowed to react'with hydrogen at 200 to 250 C. for two hours under a pressure of 200 to 300 atmospheres of hydrogen. 48.4 g. of N-dodecylpiperidine (CnHztNCuHm) B. P. 144-146/2 mm. was isolated by fractionation from the reaction mixture. 7

Example 2.50 g. of N-sebacyclpiperidine amine were also isolated.

In the table, the first column indicates the amide used; the second, the number 0! mols in the charge; the third, the amount of catalyst in grams; the fourth, the time in hours and the fifth contains the products obtained by the hydrogenation and indicates either the boiling point or melting point of these products.

a b c In the case of unsubstituted amides, the 0 linkage is most easily broken with the consequent formation of amines. In mono or di substituted amides, all three of the linkages may be broken according to conditions. For instance, in case R and R are alkyl groups, the break occurs at the a linkage much more easily and probably Table Time M013 hours Amide a? Product Yield Heptamide, M. P. 96

' -Hydroxy valeramide;

a-Phenyl butyramide, M. P. 72-80" N-n-amyl lauramlde N-di-ethyl lauramide.

N-di-ethyl heptamide, B. P. 106-7/2 mm.

N-B-phenylethyl heptamide 0. 23 0.3

N-phenyl lauramide 0. l8 3. 25

N-cyclohexyl-lauremide 0. 20

Salicylamide, M. P. 137 Succinamide, M. P. 252;

N-n-amyl-adipamide Tetrahydroiuroamlde, M. P. 76-8 N -n-amyl succinimid N -p-phenylethyl succinimide N-n-amyl phtlialimide, B. P. 152/2 mm N-B-phenylethylphthalimid, M. P. lilo-131.

N-heptoyl piperidine Nonanoyl piperidine B-Hydroxy buty'ryl piperidineaa Dimethyl-B-hydroxy butyryl p a-Phenyl butyryl piperidine Succinyl piperidine, M. P. 68-69 Adipyl piperidine Benzoyl piperidino, B. P. 15l2/3 mm Furoyl piperidine, M. P. 58-9 Ammonium laurate Di-N-B-phenylethyl lauramide m H on a.o a: -z,o cou ua: o a o eno go 9 g-- -o o The time in the above table is calculated from the time at which the temperature of the material in the bomb reached 250 C. In some instances the hydrogenation was complete by the Di-n-dodecylarnine n-lileptylamine, B. P. 149l53/740 mm Di-n-heptylamine, 1346/9 mm Valerolactone, B. P. 968/l3 mm 4-hydroxy-l-amino pentane, B. P. l19l2l/8 mm. 2-phenyl-1-aminobutane, B. P. l056/3 111111.... Products boiling, l63l67/3-4 mm Di-n-amylamine, 6 p. 8/25 mm n-Dodecylamine, l358/l0 mm n-Dodecyl-n-amylamine, B. P. 1757/l0 mm D1-n-decylamine n-Dodecyl-ethylamine, B. P. 1249/2 mm Di-n-dodecylamine, M. P. til-53 n-Heptylethylarnine, b. p. 8l3/16 mmn-Heptyldiethylamine, 86 7/l6 mm.-.. Di-n-heptylamine, 129-36/9 mm Ethyl benzene. n-Heptyl amine, B. P. l4752f740 mm fl-Phenyl ethylamine, 80-4/l0 mm Di-n-heptyl amine, l3l6/9 mm n-Heptyl-fl-phenylethylamine, 15l7/9 mm- Aniline B. P., 5865/9 mm Di-phenylarnine, l09l2/2 mm., M n-Dodecylamine, 1l9120/2 mm n-Dodecylphenylamine, l601/2 Percent n-Dodecyclohexylamine, 1589/2 mm. Di-n-dodecylamine, M. P. 53- o-Cresol, B. P. 77- J/i0 mm Pyrrolidine (isolated as the hydrochloride) N-4-am1no-n-butyl pyrrol-idine, B. P. 83-5/8 mm. N-4-amino-n-butyl succinmide, -4l3 mm.. Din-amylamine, B. P. 95-9/l3 mm Tetl'ehydrofurfurylamine 646/8 mm Di-tetrahydrofurfurylamlne. l26-8/9 mm. N-n-amyl pyrrolidine, 1747/740 Ethyl benzene, l39-3/740 N-Bphenylethyl pyrrolidine, ll3-l5/9 mm 8-fl 1 Hexahydrobenzopyrrolidine, 65-70/8-9 mm N-n-amyl flfl hexahydrobenzopyrrolidine, 104-6/3 mm- Ethyl benzene l346/740 mm 8-13 1 Hexahydrobenzopyrrolidlne, 65-70/9 mm. fl-gPhenylethyb-fl, B hexahydrobenzopyrrolidine, -8/

mm. Heptyl alcohol 7080/9 mm N-n-heptyl piperidine, 1024 [9 mm- N-n-nonyl piperidine, l357/1l mm-.- Butyl piperidine, -170/740 mm PlIl8l'ld1n9..... Iso-butyl piperidine, 159-61/740 2-phenyl but-.inol-l, ll24/8 mm 1-p1peridino-2-phonyl butane, l34-5/8 m Butandiol 1-4, ll3 20l8 mm 1-4 dipiperidino butane l33l3 Hexandiol 1-6, 1268/2 mm 1-6 dipiperidino hexane, 147

Dodecyl-di-fi-phenylethylamine to the exclusion of a break at the b linkage. This may be seen from the proportion of products obtained from N-n-amyl lauramide, N-diethyl lauramide and N-diethyl heptamide. In cases where R is a cyclohexyl or betaphenyl ethyl group, the break occurred predominantly at but a considerable amount occurred also at b. When R is phenyl the break at the "b" linkage predominates.

The pressures and temperatures given in the foregoing examples are the preferred temperatures. The hydrogenation, however, may be carried out under other conditions and we have found that the pressure may be varied from 50 to about 500 atmospheres and the temperatures from 150 to about 350 C.

The process may also be carried out in a continuous flow system with equally good results.

This application is a continuation-in-part of prior application Serial No. 556,710 filed August 12, 1931.

I claim:

1. The process of hydrogenating amides comprising treating them with hydrogen at hydrogenating temperatures and pressures in the presence of, as a catalyst, an oxide of a hydrogenating metal,

2. The process of hydrcgenating amides comprising treating them with hydrogen at hydrogenating temperatures and pressures in the presence of, as a catalyst, an oxide oi a hydrogenating metal and an oxide of an acidforming metal.

3. The process of hydrogenating amides comprising treating them with hydrogen at hydro genating temperatures and pressures in the presence of, as a catalyst, an oxide of a hydrogenating metal, an oxide of an acid-forming metal, and an oxide of one of the group consisting of barium, calcium and magnesium.

4. The process of hydrogenating amides comprising treating them with hydrogen at hydrogenating temperatures and pressures in the presence of, as a catalyst, copper oxide and chromium oxide.

5. The process of hydrogenatlng amides com-,

prising treating them with hydrogen at hydrogenating temperatures and pressures in the presence of, as a catalyst, copper oxide, chromium oxide, and barium oxide.

6. The process of hydrogenating amides comprising treating them with hydrogen at hydrogenating temperatures and pressures in the presence of, as a catalyst, an oxide of a hydrogenating metal, and an inert liquid which is a solvent for water and the amide,

7. The process of hydrogenating amides comprising treating them with hydrogen at hydrogenating temperatures and pressures in the presence of, as a catalyst, an oxide of a hydrogenating metal, and a liquid which is a solvent for water and the amide, said liquid being inert chemically towards the amide and its hydrogenation products.

8. The process of hydrogenating amides comprising treating them with hydrogen at hydrogenating temperatures and pressures in the presence of, as a catalyst, an oxide of a hydrogenating metal, and dioxane.

9. The process of hydrogenating amides comprising treating them with hydrogen at hydrogenating temperatures and pressures in the presence of dioxane and, as a catalyst, an oxide of a hydrogenating metal and an oxide of an acidforming metal.

10. The process of hydrogenating amides comprising treating them with hydrogen at hydrogenating temperatures andd pressures in the presence of dioxane and, as a catalyst, an oxide of a hydrogenating metal, an oxide of ,an acidforming metal, and an oxide of one of the group consisting of barium, calcium and magnesium.

11. The process of hydrogenating amides comprising treating them with hydrogen at temperatures 01 from 150 to 350 degrees C. and pressures of from 50 to 500 atmospheres in the presence oi, as a catalyst, an oxide of a hydrogenating metal.

12. The process of hydrogenating amides comprising treating them with hydrogen at temperatures of from 150 to 350 degrees C. and pressures of from 50 to 500 atmospheres in the presence of, as a catalyst, an oxide of a hydrogenating metal and an oxide of an acid-forming metal.

13. The process of hydrogenating amides comprising treating them with hydrogen at temperatures of from 150 to 350 degrees C. and pressures ofrrom 50 to 500 atmospheres in the presence of, as a catalyst, on oxide of a hydrogenating metal, an oxide of an acid-forming metal, and an oxide of one of the group consisting of barium. calcium and magnesium.

14. The process of hydrogenating amides comprising treating them with hydrogen at temperatures of from 150 to 350 degrees C. and pressures of from 50 to 500 atmospheres in the presence 01', as a catalyst, copper oxide, chromium oxide and barium oxide.

15. The process of hydrogenating amides comprising treating them with hydrogen at temperaturesoi' from 150 to 350 degrees C. and pressures of from 50 to 500 atmospheres in the presence of dioxane and, as a catalyst, an oxide of a hydrogenating metal.

16. The process of hydrogenating amides comprising treating them with hydrogen at temperatures of from 150 to 350 degrees C. and pressures of from 50 to 500 atmospheres in the presence of dioxane and, as a catalyst, an oxide of a hydrogenating metal and an oxide of an acidiorming metal.

1'7.- The process of hydrogenating amides comprising treating them with hydrogen at temperatures of from 150 to 350 degrees C. and pressures of from 50 to 500 atmospheres in the presence of diozane and, as a catalyst, an oxide 0! a hydrogenating metal, an oxide of an acid-forming metal and an oxide of one of the group consisting of barium, calcium and magnesium.

18. The process of preparing amines which comprises treating an acid amide with hydrogen at hydrogenating temperatures and pressures in the presence of an inert solvent and, as a catalyst, an oxide of a hydrogenating metal.

19. The process of preparing amines which comprises treating the'ammonium salt of anorganic acid with hydrogen at hydrogenating temperatures and pressures in the presence of an inert solvent and, as a catalyst, an oxide of a hydrog'enating metal.

20. The process of hydrogenating the unsubstituted carboxylic acid amide of a soap-forming fatty acid which comprises heating said amide, in an inert organic solvent, at a temperature of about 250 C. and at a pressure of about 200 atmospheres with hydrogen in the presence of a copper oxide hydrogenation catalyst.

21. The process of producing amines, which comprises heating a compound selected from the group consisting of carboxylic acid amides and carboxylic acid lmides, while admixed with hydrogen, to a temperature in excess of 200 C., at a pressure between about 50 and about 500 atmospheres and in the presence of an oxide of a hydrogenating metal and an oxide of an acidforming metal.

22. The process of producing amines, which comprises heating a compound selected from the group consisting of carboxylic acid amides and carboxylic acid imides, while admixed with hydrogen, to a temperature in excess of 200 C., at a pressure between about 50 and about 500 atmospheres and in the presence of an oxide of a hydrogenating metal, an oxide of an acid forming metal, and magnesium oxide.

23. The process of producing amines, which comprises heating a compound selected from the group consisting of carboxylic acid amides and carboxylic acid imides, while admixed with hydrogen to a temperature in excess of 200 C., at a pressure between about 50 and about 500 atmospheres in the presence of a hydrogenation catalyst.

24. The process of claim 23 characterized in that the process is carried out in an inert water miscible organic medium.

25. The process of claim 23 characterized in that the process is carried out in dioxane.

26. The process of hydrogenating a phthalimide which comprises heating said imide at about 250 C. under a pressure of from about 50 to about 500 atmospheres with hydrogen in the presence of a copper oxide hydrogenation catalyst.

27. The process which comprises hydrogenating succinamide at about 250 C. under a pressure of from about 50 to about 500 atmospheres with hydrogen in the presence of a copper oxide hydrogenation catalyst.

HOMER ADKINS. 

